Platelets from patients with acute myocardial ischemia are hyperactive and resistant to the antiaggregatory effect of prostacyclin/prostaglandin E1. We have shown that this resistance is due to decreased binding of PGE1 to platelets secondary to a decrease in the prostanoid receptor numbers. The impaired prostaglandin binding of these platelets could be "normalized" in approximately 70% of cases by incubating these cells with physiological concentrations of insulin. We propose to investigate: 1) the status of insulin receptors of platelets from those patients responding to insulin to establish that the prostaglandin-insulin interaction is modulated by the occupancy of the insulin receptors by the hormone; 2) The status of the insulin receptors of platelets from those patients not responding to insulin, and to relate whether the failure of response to insulin challenge is due to defective insulin receptors and, thus, interferes with the insulin-prostacyclin interaction; 3) whether the improvement of prostaglandin E1 binding to platelets by insulin, added in vitro, can be achieved by in vivo infusion of the hormone to patients with acute myocardial infarction. Investigations will be carried out to determine the status of insulin receptors of platelets and the plasma insulin level to correlate to the prostaglandin receptor activity during acute myocardial ischemia and during recuperation. Assessments will be made whether a possible dysfunction of the hormone receptor is platelet specific or might be related to defective insulin receptors of target cells in general by determining the hormone receptor activity of the patients' erythrocyte membrane and compare it with that of normal red cell ghosts. The effect of insulin on the activation of adenylate cyclase and the increase of cyclic AMP formation, due to increased autacoid binding to the platelets, will be compared wit normal platelets to determine any impairment of post-receptor interaction events in the synthesis of the nucleotide. These experiments will help to understand whether the increased binding of PGE1 to platelets of patients by insulin relates to the increased formation of cyclic AMP. Further, the effect of insulin on the improved prostaglandin binding to platelets will be investigated to determine functional modification of sensitivity of these cells to aggregating agents when the peptide hormone is administered in vitro or in vivo. The recognition, that the impaired activity of prostacyclin during myocardial ischemia can be improved by insulin might have important implications, since platelet aggregates and thrombi frequently are the final cause for ischemic events.